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A randomised, placebo-controlled, single-blind study to characterise the biomarker effects of the CSF-1 receptor antagonist JNJ-40346527 in participants with mild cognitive impairment.

Phase 1
Conditions
Mild Cognitive Impairment
MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Registration Number
EUCTR2018-004149-17-GB
Lead Sponsor
niversity of Oxford / Clinical Trials and Research Governance
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Not specified
Target Recruitment
54
Inclusion Criteria

- Any gender over and including 50 years old
- Willing and able to provide informed consent
- CDR Global score = 0.5
- Self and/or study partner report and impairment on objective cognitive tasks (performance on Hopkin’s verbal learning task (HVLT) – delay recall and/or free recall > 1 standard deviation (SD) below mean for age/education level).
-Study Partner available, that spends at least 4 hours per week with the participant. The Study Partner must be willing and able to assist with the CDR interview, and will be provided with their own Information Sheet and Informed Consent form.
- Able to read and write in English and with 7 minimum years formal education
- Be considered eligible according to TB screening criteria
- Be healthy on the basis of clinical laboratory tests performed at screening.
- Women must be postmenopausal
- Men who are heterosexually active must agree to use a double-barrier method of birth control and to not donate sperm during the study and for 6 months after last dose
- Be willing to adhere to all of the procedures, prohibitions amd restrictions specified in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

•Research participants who fulfil diagnostic criteria for any type of dementia (e.g. Alzheimer Dementia, Frontotemporal Dementia (FTD), Diffuse Lewy Body Dementia (DLBD), Vascular Dementia (VAD), etc)
CDR =1.
•Known carriers of a presenilin 1 (PSEN1), presenilin 2 (PSEN2) or APP mutation associated with Autosomal Dominant AD or any other neurodegenerative disease.
•Prohibited or restricted concomitant medication as detailed in Section 10.1.7 in the protocol.

•Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre-manifest Huntington’s disease, multiple sclerosis, Parkinson’s disease, Down syndrome, active alcohol/drug abuse or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder. To quantify abuse is to define this as history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-V) criteria within 6 months before screening or positive test result for alcohol and/or drugs of abuse at screening/admission.
•History of latent or active infection of one of the following infectious diseases at screening: Listeria infection, Histoplasma, Coccidioides, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, Aspergillus, cytomegalovirus generalised or Herpes zoster infection
•Any cancer or history of cancer in the preceding 5 years (excluding cutaneous basal or squamous cell cancer resolved by excision).
•Any conditions that are clinically significant and may deem the participant’s participation in an investigational trial unsafe, e.g., symptomatic cardiovascular disease (including re-vascularisation procedures within the previous year), severe renal or hepatic failure, any clinically relevant abnormalities in blood parameters included in local routine assessments, severe loss of vision, hearing or communicative ability, conditions preventing co-operation or completing the required assessments in the trial, as judged by the Investigator.
•Any contraindications for PET/MRI scanning.
•Any contraindications for Lumbar Puncture.
•Any evidence of intracranial pathology which may affect cognition including but not limited to brain tumours (benign or malignant), aneurysm or arteriovenous malformations, territorial stroke (excluding smaller watershed strokes), history of or recovering haemorrhage (parenchymal or subdural), or obstructive hydrocephalus. Research participants with an MRI scan demonstrating markers of small vessel disease (e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant, or microbleeds are allowed.
•Participation in a clinical trial with an Investigational Medicinal Product (IMP) in the last 30 days or 90 days in case of biologics.
•Diminished decision-making capacity that renders the individual not capable of consenting.
•Any other factors in the opinion of the Investigator that could contraindicate the participation of the research participant into this trial.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
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